The trabecular meshwork (TM) is a region of spongy tissue in the eye located around the base of the cornea and near the ciliary body. The TM functions to drain the aqueous humor from the eye into the circulatory system via the anterior chamber and a series of tubes called Schlemm's canal. In addition to producing and secreting extracellular matrix proteins and proteolytic enzymes, cells of the TM (i.e., TM cells) phagocytose extracellular debris to prevent blockage of Schlemm's canal. Decreased TM cellularity and impaired TM function lead to the pathogenesis of glaucoma, a medical condition of the eye in which aqueous humor outflow is decreased and/or levels of aqueous are increased, either or both of which ultimately lead to an elevation in intraocular pressure.
Current treatments for glaucoma include medications, laser treatment, or surgical treatment. Laser trabeculoplasty is a surgery in which a laser makes tiny, evenly spaced burns in the TM to re-stimulate its drainage function. Laser trabeculoplasty surgery increases cell division in the TM, thereby increasing TM cellularity. Within days of the procedure, cells found in the anterior, non-filtering region of the TM, called the insert area, migrate out of this region and repopulate the laser-burned sites. While laser trabeculoplasty is a quick, easy, convenient, and relatively low-risk procedure, there are drawbacks to this technique. For example, about half of the patients require further medical or surgical treatment within two to five years. Also, for example, the procedure has a relatively small effect on lowering the eye pressure and repeat treatments are usually not very effective. In some people, such as individuals with glaucoma from eye inflammation or eye trauma, the procedure has no benefit and can even worsen the glaucoma.
Surgical treatment options for glaucoma, such as trabeculectomy, also have risks. In some cases, the glaucoma operation fails and requires glaucoma medication or another glaucoma operation. Frequently, the eye pressure becomes severely reduced immediately after surgery. While this is harmless over a short period of time, this can lead to vision changes if the reduced eye pressure continues over a long period of time. Also, surgery treatment most often requires general anesthesia. Further, a leak from the surgery, bleeding in the eye, or infection of the eye can occur post˜surgery.
Alternatively, the application or administration of stem cells that have the potential to differentiate into TM cells is an attractive means of treating or preventing glaucoma. It has been postulated that the insert area contains stem-like cells that serve as a source of TM cell renewal, and some groups report attempts to isolate such cells through surgical dissection of the TM insert area. However, Kelley et al., Exp Eye Res 88(4); 747-751 (2009) concede that this method represents a difficult technique. Other groups have cultured TM cells or have produced neurospheres from human TM cultures with an aim to isolate multipotent progenitor cells from the TM. While these groups report the expression profiles of the isolated cells, none have demonstrated that the isolated cells are capable of differentiating into TM cells.
In view of the foregoing, there exists a need in the art for isolated populations of multipotent stem cells that are capable of differentiating into TM cells and non-invasive, efficient methods of obtaining such populations.